The objective of this research proposal is to elucidate the cellular and regulatory mechanisms responsible for aberrant IgE biosynthesis in human atopy. Culturing fractionated peripheral blood lymphocytes (PBL) from normal and rye grass sensitive individuals, I will assess in vitro, the abilities of T-helper and T-suppressor subpopulations to regulate the production of total IgE and rye grass-specific IgE antibodies which are produced by pokeweed mitogen-responsive or lymphoblastoid B cells. I will purify the rye grass antigens, rye group I (R) and adapt the quantitative radioimmunoassay to measure extremely low levels (approximately 150 pg/ml) of R-specific IgE produced in vitro and in vivo by atopics and normals. Next I will assess in vitro the ability of T regulatory, accessory, and P cells from PBL of normals and atopics to interact and produce a given total IgE and R-specific IgE response. With PBL from patients receiving immunotherapy, I will follow in vitro the effects of therapy to determine what cellular or regulatory changes occur in relation to changes in serum antibodies. Additionally, I will examine atopic sera for the presence of autoantibodies or other serum factors which may have a role in faulty IgE synthesis. Last, I will probe R-specific antibody specifications of IgG and IgE stimulated in an R-atopic person and determine if distinct epitopes on the same allergen molecule stimulate different classes of antibody.